Imaging the Interplay Between Axonal Damage and Repair in Multiple Sclerosis

NCT ID: NCT05177523

Last Updated: 2024-12-16

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 300 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-09-04
• Study Completion Date: 2028-12-31

Brief Summary

This project is to:

1. Quantify differences in axonal integrity and organization in aMS versus naPMS patients.

2. Quantify changes in axonal integrity and organization in aMS versus naPMS patients over a two-year period.

3. Validate the combination of imaging parameters that best differentiate aMS versus naPMS patients using histopathology.

Detailed Description

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system characterized by multifocal inflammatory infiltrates, microglial activation and degradation of oligodendrocytes, myelin and axons. Clinical MS categories exhibit variable amount of central nervous system (CNS) damage and repair, depending on numerous variables including genetic, immunological, pathological and environmental factors.

Therefore, understanding the interplay between axonal damage (i.e. axonal demyelination/degeneration/loss/disorganization) and (ii) axonal repair (i.e. axonal remyelination/reorganization) in living MS patients may be the key to understand disease progression, to establish accurate disease monitoring criteria and to predict disease response to future reparative therapies. New in-vivo methods are necessary to elucidate the interplay between axonal damage and repair in the brain of living patients with MS. Advanced MRI (aMRI) permits a multifaced quantification of the various components of the axons and their organization. Neurite Orientation Dispersion and Density Imaging (NODDI) and Diffusion Kurtosis (DK) are new approaches in clinical research This study is to identify in vivo the specific neuropathological pattern of axonal damage and repair exhibited by active MS (aMS) and non-active progressive MS (naPMS) patient by leveraging the information provided by model-based diffusion metrics (NODDI, DK), Magnetization Transfer Imaging (MTI), Multi-echo Susceptibility-Based imaging (SBI), Myelin Water Imaging (MWI) and quantitative T1 relaxometry (qT1). These advanced MRI contrasts provide complementary and partially redundant information about the axonal structure and its organization (i.e. density and orientation of axons and dendrites in the brain tissue, axonal integrity and myelination, presence of myelin and iron, and brain tissue architecture). Therefore, their combination may prove high sensitivity and specificity to axonal damage and repair.

This project has 3 main aims:

Aim 1. Quantify differences in axonal integrity and organization in aMS versus naPMS patients.

Aim 2. Quantify changes in axonal integrity and organization in aMS versus naPMS patients over a two-year period.

Aim 3. Validate the combination of imaging parameters that best differentiate aMS versus naPMS patients using histopathology.

Conditions

Multiple Sclerosis (MS); Relapsing-remitting Multiple Sclerosis (RRMS); Secondary-progressive Multiple Sclerosis (SPMS); Primary Progressive Multiple Sclerosis (PPMS)

Keywords

axonal damage; axonal demyelination; axonal degeneration; axonal loss; axonal disorganization; axonal repair; axonal remyelination; axonal reorganization; Advanced MRI (aMRI); Neurite Orientation Dispersion and Density Imaging (NODDI); Diffusion Kurtosis (DK); Magnetization Transfer Imaging (MTI); Multi-echo Susceptibility-Based imaging (SBI); Myelin Water Imaging (MWI); T1 relaxometry (quantitative T1, qT1); machine learning technique

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

MS patient group

Recruitment of 200 MS patients at the MS Clinic of the Department of Neurology (Neurologische Klinik und Poliklinik), University Hospital Basel (Universitätsspital Basel)

MRI

Intervention Type: DIAGNOSTIC_TEST

Each enrolled subject will undergo a MRI at baseline and a second MRI at 2 years (+/- 3 months) follow-up.

blood sampling

Intervention Type: OTHER

Each enrolled subject will undergo a blood sampling (10 ml) at baseline

control group (HC)

Recruitment of 100 healthy controls (HC) by public announcements (i.e. advertisement/flyer) on the University Hospital's and the University's notice board.

MRI

Intervention Type: DIAGNOSTIC_TEST

Each enrolled subject will undergo a MRI at baseline and a second MRI at 2 years (+/- 3 months) follow-up.

Neurocognitive examination for healthy subjects

Intervention Type: OTHER

Neurocognitive examination for healthy subjects will be performed at both baseline and follow-up

blood sampling

Intervention Type: OTHER

Each enrolled subject will undergo a blood sampling (10 ml) at baseline

Interventions

MRI

Each enrolled subject will undergo a MRI at baseline and a second MRI at 2 years (+/- 3 months) follow-up.

Intervention Type: DIAGNOSTIC_TEST

Neurocognitive examination for healthy subjects

Neurocognitive examination for healthy subjects will be performed at both baseline and follow-up

Intervention Type: OTHER

blood sampling

Each enrolled subject will undergo a blood sampling (10 ml) at baseline

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Patients may be diagnosed with:

1. active RRMS (n=100): Relapsing-remitting course and > 1 clinical relapse and/or signs of MRI activity (> 1 Gd enhancing lesion) during the last year before study enrollment.

2. non-active PMS (n=100): Progressive course (PPMS or SPMS) and no clinical relapses and/or signs of MRI activity during the last year before study enrollment.

• Age 18-80 years old
• No other neurological or psychiatric disorder

• Age 18-80 years old
• No other neurological or psychiatric disorder

Exclusion Criteria

• Pregnancy
• Contraindication to MRI (eg, claustrophobia, metallic implants, pacemaker etc).
• Inability to give consent

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Swiss National Science Foundation

OTHER

Sponsor Role: collaborator

University Hospital, Basel, Switzerland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Cristina Granziera, Prof. Dr. med.

Role: PRINCIPAL_INVESTIGATOR

Department of Neurology, University Hospital Basel

Locations

University Hospital Basel, Department of Neurology

Basel, , Switzerland

Site Status: RECRUITING

Countries

Switzerland

Central Contacts

Cristina Granziera, Prof. Dr. med.

Role: CONTACT

Phone: +41 61-32 85 665

Email: cristina.granziera@usb.ch

Facility Contacts

Cristina Granziera, Prof. Dr. med.

Role: primary

Other Identifiers

2018-01174; me18Granziera

Identifier Type: -

Identifier Source: org_study_id